scholarly journals PLGA Nanoparticle-Based Formulations to Cross the Blood–Brain Barrier for Drug Delivery: From R&D to cGMP

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 500
Author(s):  
Kaining Zhi ◽  
Babatunde Raji ◽  
Anantha R. Nookala ◽  
Mohammad Moshahid Khan ◽  
Xuyen H. Nguyen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Good Manufacturing Practice ◽  
Plga Nanoparticles ◽  
Pharmaceutical Products ◽  
Brain Barrier ◽  
Poly Vinyl Alcohol ◽  
Blood Brain

The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that is used in Food and Drug Administration (FDA)-approved pharmaceutical products and medical devices. PLGA nanoparticles (NPs) have been reported to improve drug penetration across the BBB both in vitro and in vivo. Poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poloxamer (Pluronic) are widely used as excipients to further improve the stability and effectiveness of PLGA formulations. Peptides and other linkers can be attached on the surface of PLGA to provide targeting delivery. With the newly published guidance from the FDA and the progress of current Good Manufacturing Practice (cGMP) technologies, manufacturing PLGA NP-based drug products can be achieved with higher efficiency, larger quantity, and better quality. The translation from bench to bed is feasible with proper research, concurrent development, quality control, and regulatory assurance.

PLA/PLGA nanoparticles for delivery of drugs across the blood-brain barrier

2013 ◽  
Vol 2 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Jingyan Li ◽  
Cristina Sabliov
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Drug Carrier ◽  
Plga Nanoparticles ◽  
Brain Barrier ◽  
Poly Lactic Acid ◽  
Blood Brain

AbstractThe blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease. Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable PLGA and poly (lactic acid) (PLA) NPs for drug delivery across the BBB. Recent advances on PLGA/PLA NPs enhanced neural delivery of drugs are reviewed in this paper. Both in vitro and in vivo studies are included. In these papers, enhanced cellular uptake and therapeutic efficacy of drugs delivered with modified PLGA/PLA NPs compared with free drugs or drugs delivered by unmodified PLGA/PLA NPs were shown; no significant in vitro cytotoxicity was observed for PLGA/PLA NPs. Surface modification of PLGA/PLA NPs by coating with surfactants/polymers or covalently conjugating the NPs with targeting ligands has been confirmed to enhance drug delivery across the BBB. Most unmodified PLGA NPs showed low brain uptake (<1%), which indirectly confirms the safety of PLGA/PLA NPs used for other purposes than treating CNS diseases.

scholarly journals A Multifunctional AIE Nanoprobe as a Drug Delivery Bioimaging and Cancer Treatment System

2021 ◽  
Vol 9 ◽  
Author(s):  
Keqi Hu ◽  
Daquan Zhou ◽  
Linlin Rao ◽  
Peng Wang ◽  
Chunxiang Xiang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Nasopharyngeal Cancer ◽  
Brain Barrier ◽  
Cancer Drug ◽  
Blood Brain ◽  
Progression Of Disease ◽  
Good Biocompatibility

Of all malignant brain tumors, glioma is the deadliest and most common, with a poor prognosis. Drug therapy is considered as a promising way to stop the progression of disease and even cure tumors. However, the presence of blood brain barrier (BBB) and blood tumor barrier (BTB) limits the delivery of these therapeutic genes. In this work, an intelligent cell imaging and cancer therapy drug delivery system targeting the blood-brain barrier and the highly expressed transferrin receptors (TfR) in gliomas has been successfully constructed, and an amphiphilic polymer (PLA-PEG-T7/TPE) with aggregation-induced emission (AIE) properties has been designed and successfully synthesized. PLA-PEG-T7/TPE self-assembled polymer micelles showed significant AIE effect in aqueous solution with good biocompatibility. Therefore, it can be used for potential biological imaging applications. In addition, drug-carrying micelles showed typical behavior of regulating drug release. Inhibition of cell proliferation in vitro showed that the drug-loaded micelles had dose-dependent cytotoxicity to LN229 cells. In the in vivo anti-tumor experiment, PLA-PEG-T7/TPE/TMZ had the best therapeutic effect. These results indicated that T7 functionalized PLA-PEG was a promising platform for nasopharyngeal cancer drug combination therapy.

Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study

2017 ◽  
Vol 5 (42) ◽  
pp. 8314-8321 ◽  
Author(s):  
L. V. Nair ◽  
R. V. Nair ◽  
S. J. Shenoy ◽  
A. Thekkuveettil ◽  
R. S. Jayasree
Keyword(s):  
Drug Delivery ◽  
Brain Imaging ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Gold Cluster ◽  
Brain Barrier ◽  
Gold Nanocluster ◽  
Blood Brain

l-Dopa conjugated fluorescent gold cluster to cross undisturbed blood brain barrier for early stage imaging and drug delivery.

Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation

2005 ◽  
Vol 289 (5) ◽  
pp. H2012-H2019 ◽  
Author(s):  
Melissa A. Fleegal ◽  
Sharon Hom ◽  
Lindsay K. Borg ◽  
Thomas P. Davis
Keyword(s):  
Blood Brain Barrier ◽  
Paracellular Permeability ◽  
Cell Permeability ◽  
Brain Barrier ◽  
Cerebral Microvessels ◽  
Permeability Changes ◽  
Blood Brain ◽  
Brain Microvessel

The blood-brain barrier (BBB) is a metabolic and physiological barrier important for maintaining brain homeostasis. The aim of this study was to determine the role of PKC activation in BBB paracellular permeability changes induced by hypoxia and posthypoxic reoxygenation using in vitro and in vivo BBB models. In rat brain microvessel endothelial cells (RMECs) exposed to hypoxia (1% O2-99% N2; 24 h), a significant increase in total PKC activity was observed, and this was reduced by posthypoxic reoxygenation (95% room air-5% CO2) for 2 h. The expression of PKC-βII, PKC-γ, PKC-η, PKC-μ, and PKC-λ also increased following hypoxia (1% O2-99% N2; 24 h), and these protein levels remained elevated following posthypoxic reoxygenation (95% room air-5% CO2; 2 h). Increases in the expression of PKC-ε and PKC-ζ were also observed following posthypoxic reoxygenation (95% room air-5% CO2; 2 h). Moreover, inhibition of PKC with chelerythrine chloride (10 μM) attenuated the hypoxia-induced increases in [14C]sucrose permeability. Similar to what was observed in RMECs, total PKC activity was also stimulated in cerebral microvessels isolated from rats exposed to hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min). In contrast, hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min) significantly increased the expression levels of only PKC-γ and PKC-θ in the in vivo hypoxia model. These data demonstrate that hypoxia-induced BBB paracellular permeability changes occur via a PKC-dependent mechanism, possibly by differentially regulating the protein expression of the 11 PKC isozymes.

The Blood-Brain Barrier and Brain Drug Delivery

2006 ◽  
Vol 6 (9) ◽  
pp. 2712-2735 ◽  
Author(s):  
J. M. Koziara ◽  
P. R. Lockman ◽  
D. D. Allen ◽  
R. J. Mumper
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Present Report ◽  
Drug Carriers ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Anatomy And Physiology ◽  
Brain Drug Delivery ◽  
Blood Brain

The present report encompasses a thorough review of drug delivery to the brain with a particular focus on using drug carriers such as liposomes and nanoparticles. Challenges in brain drug delivery arise from the presence of one of the strictest barriers in vivo—the blood-brain barrier (BBB). This barrier exists at the level of endothelial cells of brain vasculature and its role is to maintain brain homeostasis. To better understand the principles of brain drug delivery, relevant knowledge of the blood-brain barrier anatomy and physiology is briefly reviewed. Several approaches to overcome the BBB have been reviewed including the use of carrier systems. In addition, strategies to enhance brain drug delivery by specific brain targeting are discussed.

Refining In Vitro Neurotoxicity Testing — The Development of Blood–Brain Barrier Models

2003 ◽  
Vol 31 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Hanna Tähti ◽  
Heidi Nevala ◽  
Tarja Toimela
Keyword(s):  
Blood Brain Barrier ◽  
Cell Lines ◽  
Three Dimensional ◽  
Brain Barrier ◽  
Culture Methods ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
In Vitro Bbb Model

The purpose of this paper is to review the current state of development of advanced in vitro blood–brain barrier (BBB) models. The BBB is a special capillary bed that separates the blood from the central nervous system (CNS) parenchyma. Astrocytes maintain the integrity of the BBB, and, without astrocytic contacts, isolated brain capillary endothelial cells in culture lose their barrier characteristics. Therefore, when developing in vitro BBB models, it is important to add astrocytic factors into the culture system. Recently, novel filter techniques and co-culture methods have made it possible to develop models which resemble the in vivo functions of the BBB in an effective way. With a BBB model, kinetic factors can be added into the in vitro batteries used for evaluating the neurotoxic potential of chemicals. The in vitro BBB model also represents a useful tool for the in vitro prediction of the BBB permeability of drugs, and offers the possibility to scan a large number of drugs for their potential to enter the CNS. Cultured monolayers of brain endothelial cell lines or selected epithelial cell lines, combined with astrocyte and neuron cultures, form a novel three-dimensional technique for the screening of neurotoxic compounds.

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